Alpha-1-antitrypsin deficiency

Homozygous PIZZ alpha 1-antitrypsin deficiency, which has an incident of 1 in 1600 to 1 in 2000 live births, is the most common genetic cause of liver disease in children. It is also associated with chronic liver disease and hepatocellular carcinoma in adults, It is a well-known cause of pulmonary e mphysema. Although emphysema is due to uninhibited proteolytic destruction of the connective tissue backbone of the lung, liver disease is thought to result from the toxic effects of the mutant alpha(1)AT molecule retained wi thin the endoplasmic reticulum of liver cells. Screening studies done by Sv eger in Sweden have shown that only 10 to 15% of the PIZZ population develo p clinically significant liver disease over the first 20 years of life, Rec ent studies have suggested that a subgroup of PIZZ individuals are predispo sed to liver injury because of an inefficient degradation of mutant alpha(1 )ATZ within the endoplasmic reticulum. Altered migration of the abnormal al pha(1)ATZ molecule in isoelectric focussing gels is the basis of the diagno sis of alpha(1)AT deficiency. Treatment of alpha(1)AT deficiency-associated liver disease is mostly supportive. Liver replacement therapy has been use d successfully for severe liver injury. An increasing number of patients wi th severe emphysema have undergone lung transplantation.